Flavonoide esters and their use notably in cosmetics

ABSTRACT

The invention relates to a flavonoid ester. This flavonoid ester results from the reaction product of at least one flavonoid selected from the group consisting of a flavonoid with a ketone group in the 4-position, a salt, ester or ether of such a flavonoid, and a C-heteroside and/or O-heteroside derivative of such a flavonoid, with the proviso that this flavonoid contains at least one free alcohol group, with an organic monoacid having from 3 to 30 carbon atoms. These flavonoid esters constitute useful active principles for the manufacture of cosmetic, dermopharmaceutical, pharmaceutical, dietetic or agri-foodstuff compositions.

This application is a division of prior application Ser. No. 09/113,158filed Jul. 10, 1998 now U.S. Pat. No. 6,235,294.

The invention relates essentially to novel flavonoid esters, to theiruse in cosmetics, dermopharmacy, pharmacy, dietetics andagri-foodstuffs, and to cosmetic, dermopharmaceutical, pharmaceutical,dietetic and agri-foodstuff compositions in which said flavonoid estersare used.

Within the framework of the invention, it has been discovered,surprisingly and unexpectedly, that specific flavonoid esters can bestabilized while at the same time preserving their initial property,particularly of free radical inhibition and enzyme inhibition, and forapplications associated with these properties:

venous tonics, agents for increasing the strength of the bloodcapillaries, inhibitors of blotchiness, inhibitors of chemical, physicalor actinic erythema, agents for treating sensitive skin, decongestants,draining agents, slimming agents, anti-wrinkle agents, stimulators ofthe synthesis of the components of the extracellular matrix, toners formaking the skin more elastic, and anti-ageing agents.

State of the art:

Flavonoids are pigments found almost universally in plants. They areresponsible for the coloration of the flowers, the fruits and sometimesthe leaves. This is the case of the yellow flavonoids (chalcones,aurones, certain flavonols) and red, blue or violet anthocyanosides.They can also contribute to coloration via their role as copigments:thus colorless flavones and flavonols copigment and protectanthocyanosides.

Flavonoids absorb in the UV and their universal presence in the foliarcuticle and the epidermal cells of leaves enables them to protect theplant tissues against the harmful effects of UV radiation.

The approximately 3000 flavonoids known have a common biosyntheticorigin and hence possess the same basic structural element, namely the2-phenylchroman linkage. They can be grouped in different classesaccording to the degree of oxidation of the central pyran ring: thus adistinction is drawn between anthocyans, 2-phenylchromones (flavones,flavonols and their dimers, flavanones and dihydroflavonols),3-phenylchromans (isoflavones and isoflavanones, etc.), 2-phenylchromans(flavans, flavan-3-ols, flavan-3,4-diols), chalcones, dihydro-chalconesand aurones.

These flavonoids can be glycosylated, in which case they are calledheterosides. The osidic moiety can be mono-, di- or tri-saccharidic. Themonoosides are formed with D-glucose, but also with D-galactose orD-allose, with pentoses (D-apiose, L-arabinose, L-rhamnose, D-xylose) orwith D-glucuronic and D-galacturonic acids. The structural variabilityincreases for the heterosides whose osidic moiety is a disaccharide ortrisaccharide, which can be linear or branched.

Two types of heterosides have been described, namely O-glycosides andC-glycosides. In the case of the O-glycosides, the bond between thegenin and the ose can be formed via any one of the phenolic hydroxyls ofthe genin, but as a general rule it is particularly the hydroxyl in the7-position of flavones and the hydroxyl in the 3-position of flavonolswhich are involved. In the case of the C-glycosides, the bond is formedbetween the anomeric carbon of the sugar and the carbon in the6-position or 8-position of the genin.

The known biological properties of flavonoids

Being potentially active on the veins, flavonoids reduce thepermeability of the blood capillaries and increase their strength. This“vitamin P” property is historically associated with the observationthat certain manifestations of scurvy which are cured by theadministration of lemon juice are not cured by the administration ofvitamin C alone. It was therefore postulated that ascorbic acid couldonly act in association with a factor “P”, identified with flavonoids.Often anti-inflammatories (apigenol, chrysin, taxifolin,8-glycosylhypolaetin, gossypin, etc.), flavonoids can be antiallergics,liver protectors (isobutrin, hispidulin, flavanolignans, etc.),antispasmodics (flavonoids from thyme, etc.), hypo-cholesterolemics,diuretics, antibacterials, antivirals and cytostatics.

They are active in the regeneration of ascorbic acid in vivo viaglutathione. More generally, flavonoids are scavengers of free radicalsformed under various circumstances:

anoxia, which blocks the electron flow upstream of the cytochromeoxidases and causes the production of the superoxide radical anion;

inflammation, which corresponds inter alia to the production ofsuperoxide anions by the membrane NADPH oxidase of the leukocytes, butalso to the production (by disproportionation in the presence of ferrousions) of the hydroxyl radical and other reactive species normallyinvolved in the phenomenon of phagocytosis;

lipidic auto-oxidation, which is generally initiated by a hydroxylradical and produces lipophilic alkoxy radicals via hydroperoxides.

Numerous flavonoids react with free radicals, thereby preventing thedegradations associated with their intense reactivity towards themembrane phospholipids.

Flavonoids: enzyme inhibitors

As a general rule, flavonoids are enzyme inhibitors in vitro:

inhibition of histidine decarboxylase;

inhibition of protein kinases;

inhibition of elastase;

inhibition of hyaluronidase, which would make it possible to preservethe integrity of the ground substance of the vascular sheaths;

non-specific inhibition of catechol O-methyltransferase, which wouldincrease the amount of catecholamines available and would thereforecause an increase in the vascular strength;

inhibition of cAMP phosphodiesterase, which could explain, inter alia,their platelet aggregation inhibiting activity;

inhibition of aldose reductase;

several flavonoids, monomeric flavonols and biflavonoids are potentinhibitors of lipoxygenase and/or cyclooxygenase, which, for manyauthors—at least as far as the inhibition of cyclooxygenase isconcerned—is directly related to their capacity to scavenge freeradicals. These properties, demonstrated in vitro, could explain, in themajority of cases, the anti-inflammatory and antiallergic activitiesrecognized by numerous authors in several drugs known to containflavonoids.

However, a number of major problems do not allow flavonoids to be usedin a large number of cosmetic, pharmaceutical, dietetic oragri-foodstuffs applications:

It is extremely difficult to dissolve flavonoids and heterosides; thus,for example, heterosides are preferentially water-soluble, but thissolubility is very low (rutoside, hesperidoside, etc.). Genins arepreferentially soluble in apolar organic solvents, but here again thissolubility is generally very low. These solubility problems cansometimes be solved by using extremely sophisticated excipients,although these are not suitable for the widespread use of flavonoids.

These flavonoids may or may not be colored, but in all cases theirantioxidizing character and their very high reactivity towards oxygen orlight makes them particularly unstable, and preparations, solutions,gels or emulsions containing them undergo spectacular color changes withtime (white emulsions which become brown with time).

The concentration of these molecules in plant extracts is generally lowand the stated activities are not systematically found in plantextracts.

Various solutions have been proposed in attempts to stabilizeflavonoids.

For example, the document WO95/21018 to CNRS describes the preparationof microcapsules having walls crosslinked with plant polyphenols inorder to stabilize the polyphenols, the polyphenols stabilized bycrosslinking preserving their initial activity.

Also, the document WO94/29404 describes compositions of polyphenolderivatives, consisting of flavan derivatives and especiallyflavan-3-ol, for the stabilization of said compositions. In practice,said document essentially proposes the use of flavanolic oligomers orprocyanolidic oligomers, abbreviated to PCO, in the form of stabilizedderivatives.

All these flavans or flavanols are unsubstituted in the 4-position ofthe flavonoid heterocycle.

Objects of the invention:

As already described in the above-cited documents of the prior art, i.e.WO95/21018 and WO94/29404, flavonoids are phenolic compounds withvaluable antioxidizing properties. The use of these compounds ishampered by the problem of their instability due to the presence ofthese free phenolic groups, which oxidize readily on contact with oxygenor light to give free radical condensation compounds responsible for theappearance of coloration, making them inappropriate for use in acosmetic application.

The main object of the present invention is to solve the new technicalproblem consisting in the provision of a solution which makes itpossible to use a particular group of flavonoids, namely those with aketone group in the 4-position, also called phenylchromones or3-pyrones, in a sufficiently stable form to be usable particularly inthe fields of cosmetics, dermopharmaceutics, pharmaceutics, dieteticsand agri-foodstuffs, while at the same time preserving the initialproperties of these flavonoids.

A further object of the invention is to provide a solution which makesit possible to use flavonoids with a ketone group in the 4-position, aswell as their salts, esters or ethers, or osidic derivatives containingat least one or several C-heteroside and/or O-heteroside linkages, informs stabilized for use especially in cosmetic, dermopharmaceutical,pharmaceutical, dietetic or agri-foodstuff compositions, without losingthe initial properties of these compounds.

A further object of the invention is not only to stabilize saidflavonoids, as well as their derivatives mentioned above, but also toprovide a lipophilic form which gives these compounds liposolubleproperties and also gives them especially a greater affinity for thecell membrane and specifically the cutaneous layers.

All these objects are achieved for the first time by the presentinvention in a simple, reliable and reproducible manner which can beused on the industrial, cosmetic, pharmaceutical, dietetic oragri-foodstuffs scale.

Thus, according to a first aspect, the present invention providesflavonoid esters which result from the reaction product of at least oneflavonoid selected from the group consisting of a flavonoid with aketone group in the 4-position, a salt, ester or ether of such aflavonoid, and such a flavonoid containing at least one or severalC-heteroside and/or O-heteroside linkages, with the proviso that thisflavonoid contains at least one free alcohol group, with an organicmonoacid having from 3 to 30 carbon atoms. This monoacid can have asaturated or unsaturated, linear, branched or cyclic chain.

The above-mentioned organic monoacid can of course be selected from allorganic monoacids with a saturated or unsaturated, linear or branchedalkyl radical having from 3 to 30 carbon atoms, preferably from 4 to 22carbon atoms.

In one advantageous embodiment of the invention, the above-mentionedorganic monoacid is selected from the group consisting of butyric acid(C4:0), valeric acid (C5:0), hexanoic acid (C6:0), sorbic acid (C6:2),ascorbic acid, lauric acid (C12:0), palmitic acid (C16:0), stearic acid(C18:0), oleic acid (C18:1), linoleic acid (C18:2), linolenic acid(C18:3), undecylenic acid (C11:1), heptanoic acid (C7), arachidonic acid(C20:4), eicosapentanoic acid (C20:5) and docosahexanoic acid (C22:6 andC24:1).

In yet another advantageous embodiment of the invention, theabove-mentioned flavonoid with a ketone group in the 4-position has thefollowing structural chemical formula (I) or (II):

in which:

the groups (OR₁) to (OR₄) are in any position on the ring;

A is a hydrogen atom, a substituent R, a group —OH or a group —OR, Rbeing as defined for the radicals R₁ to R₄;

n₁ and n₂, which are identical to or different from one another, areintegers from 0 to 4, it being possible for the total of n₁+n₂ to beequal to at most 4, corresponding to the maximum number of substitutionson the ring;

n₃ and n₄, which are identical to or different from one another, areintegers from 0 to 5, the total of n₃+n₄ being equal to a maximum of 5,representing the maximum number of substitutions on the ring; and

R₁, R₂, R₃ and R₄ are each independently a hydrogen atom, an alkyl grouphaving from 1 to 30 carbon atoms, particularly a saturated orunsaturated, linear, branched or cyclic lower alkyl group having from 1to 6 carbon atoms, an acyl group with a saturated or unsaturated,linear, branched or cyclic alkyl radical having from 1 to 30 carbonatoms, preferably from 1 to 8 carbon atoms, or a simple or complex osewhich may or may not contain alkyl or acyl groups with saturated orunsaturated, linear, branched or cyclic hydrocarbon chains having from 1to 30 carbon atoms, with the proviso that at least one of thesubstituents R is a hydrogen atom, thereby defining at least one freehydroxyl group;

and the isomers of these units.

In yet another advantageous embodiment of the invention, theabove-mentioned starting flavonoid is a non-glycosylated flavone,particularly of formula (II) given above, for example apigenol (orapigenin) or luteolol, or a glycosylated flavone, for example diosmin,orientin, saponarin or shaftoside.

In yet another advantageous embodiment of the invention, the startingflavonoid is a non-glycosylated flavonol, particularly of formula (II)given above, for example kaempferol or quercetol (or quercetin), or aglycosylated flavonol, for example rutin, quercitroside, hyperoside,isoquercitroside or tiliroside.

In yet another advantageous embodiment of the invention, the startingflavonoid is a non-glycosylated or glycosylated dihydroflavonol,particularly of formula (II) given above, for example dihydrokaempferolor dihydroquercetol.

In yet another advantageous embodiment of the invention, the startingflavonoid is a non-glycosylated flavanone, particularly of formula (I)given above, for example naringetol (or naringenin), eriodictyol,hesperitin, eucalyptin, cirsimaritin, cajaflavanone, hinokiklavone,amentaflavone or bilobetol, or a glycosylated flavanone, for examplehesperidin or naringin.

In yet another advantageous embodiment of the invention, the ose oroside substituting the above-mentioned flavonoid is selected fromrhamnose, galactose, glucose and arabinose, which may or may not besubstituted, the heteroside preferably being selected from tiliroside,orientin, shaftoside, saponarin, rutin, hesperidin and diosmin.

The flavonoid esters according to the invention could be prepareddespite the much lower reactivity of the derivatives which have a ketonegroup in the 4-position, compared with those described in the prior artwhich do not have this ketone group; furthermore, the products of theinvention have a particularly high stability while at the same timeretaining their initial property, an observation which is totallyunexpected and not obvious to those skilled in the art.

Moreover, the compounds of the invention have a lipophilic activity,giving them a liposoluble character and, specifically, an affinity forthe cell membranes and particularly the tissues of the epidermis, whichagain is totally surprising.

According to a second aspect, the present invention also covers the useof the flavonoid esters according to the invention as cosmetic agentsand as active principles for the manufacture of cosmetic,dermopharmaceutical, pharmaceutical, dietetic or agri-foodstuffcompositions.

According to a third aspect, the present invention also covers acomposition, selected especially from the group consisting of a cosmeticcomposition, a dermopharmaceutical composition, a pharmaceuticalcomposition, a dietetic composition and an agri-foodstuff composition,which comprises, as one of its active agents, at least one flavonoidester as defined above. These compositions are advantageously freeradical inhibiting and enzyme inhibiting compositions; furthermore,especially in the context of a cosmetic, pharmaceutical oragri-foodstuffs application, these compositions can be used, dependingon the particular case and the particular person, for carrying out atonic treatment for the veins, a treatment for increasing the strengthof the blood capillaries, an inhibiting effect on blotchiness, aninhibiting effect on chemical, physical or actinic erythema, a treatmentfor sensitive skin, a decongesting effect, a draining effect, a slimmingeffect, an anti-wrinkle effect, a stimulating effect on the synthesis ofthe components of the extracellular matrix of the epidermis, a toningeffect on the epidermis, an improving effect on the elasticity of theskin and an anti-ageing effect on the skin.

The compositions according to the invention can be applied topically, itbeing advantageous also to use an appropriate vehicle, excipient orcarrier, particularly one which is cosmetically, dermopharmaceuticallyor pharmaceutically acceptable, or a vehicle, excipient or carrierappropriate for use in dietetics or agri-foodstuffs.

Such vehicles, excipients or carriers are well known to those skilled inthe art and are also apparent from the Formulation Examples discussedbelow. Reference may also be made to the excipients mentioned in thedocument WO95/21018, Examples 38-40, or the document WO94/29404,Examples 19-23, which are incorporated here by way of reference.

Within the framework of the invention, as all the initial biologicalproperties of the flavonoids are preserved, all the biologicalproperties stated above are claimed as forming part of the presentinvention in the context of the flavonoid esters of the invention.

The invention also covers a process for the synthesis of theabove-mentioned flavonoid esters, which comprises the acylation of atleast one flavonoid selected from the group consisting of a flavonoidwith a ketone group in the 4-position, a salt, ester or ether of such aflavonoid, and such a flavonoid containing at least one or severalC-heteroside and/or O-heteroside linkages, with an organic monoacidhaving from 3 to 30 carbon atoms.

The conditions under which such acylations are carried out are wellknown to those skilled in the art; they can be carried out chemically(solvents) or enzymatically (lipase(s) in an anhydrous medium).

In another embodiment of the invention, this acylation can be carriedout on one or more or even all of the alcohol groups of the flavonoid.This acylation can be carried out by various chemical methods ofsynthesis well known to those skilled in the art.

A first method consists in performing a chemical reaction which enablesat least one free —OH group to be replaced with an acyl radical of thetype —OCOR.

The acylating agent can advantageously be selected from acids of theformula RCOOH and the derivatives of such acids, particularly the acidhalides of the formula RCOHal, the anhydrides of the formula RCOOCR orthe esters of the formula RCOOR′, R being for example a C₁-C₃₀ alkylradical and R′ preferably being a C₁-C₆ alkyl radical.

If an acid is used as the acylating agent, the reaction can be carriedout in the presence of an activating agent for said acid, saidactivating agent normally being selectable from dicyclohexylcarbodiimideand tert-butyl chloroformate, which makes it possible to form a mixedanhydride.

The acylation reaction can be carried out in conventional manner in thepresence of a solvent to allow partial solubilization of the startingpolyphenolic compounds.

Appropriate solvents are selected for example from aromatic solventssuch as toluene, an amine such as pyridine, a halogenated derivativesuch as chloroform and an oxygenated solvent such as acetone.

The reaction is preferably carried out at a temperature equal to atleast 60° C. or, preferably, at the reflux temperature of the solvent,for a sufficient period of time to effect the acylation.

Within the framework of the invention, the acylation reaction is muchmore difficult to carry out than in the case of flavonoids which do nothave ketone substitution in the 4-position of the heterocycle, so thoseskilled in the art did not expect to be able to prepare such esters,that they would be stable and that they would preserve the initialactivity of the flavonoids, without degradation of these flavonoids,despite the unfavorable reaction conditions.

Within the framework of the invention, the starting flavonoids arepreferably reacted after solubilization in one of the organic solventsmentioned above, such as toluene, chloroform, pyridine or acetone, theacylating agent itself being dissolved in this organic phase.

Phase transfer agents can advantageously be used to facilitate thereaction, examples being halides or hydroxides, such ashalogenosulfates, for example tetrabutylammonium halogenosulfates, orbenzyltriethylammonium chloride. The reaction is carried out in thepresence of a base in order to activate the hydroxyl groups. Bases areselected for example from organic bases such as pyridine, or inorganicbases such as sodium or potassium carbonate, particularly in the form ofa saturated aqueous solution.

It is then easy to recover the resulting acylated derivative,constituting the flavonoid ester according to the invention, from thereaction mixture by decantation of the phases and treatment of each ofthe phases in order to recover the total amount of flavonoid esterformed.

Within the framework of the invention, the yields obtained are generallyvery good and can be of the order of 50% or more, the few exceptionsbeing when it is desired to prepare monoacylated derivatives.

The starting flavonoids are generally commercially available products.

However, these substances can be extracted from plants in a manner knownto those skilled in the art. The purified fractions are preferred andattempts have been made to extract therefrom the flavonoids with aketone group in the 4-position.

Within the framework of the invention, it is advantageous to use theflavonoids containing at least one or several C-heteroside andO-heteroside linkages. Examples of the oses are rhamnose, galactose,glucose and arabinose, which may or may not be substituted, theheteroside preferably being selected from tiliroside, orientin,shaftoside, saponarin, rutin, hesperidin and diosmin, without implying alimitation.

The esters of the invention afford effective protection of the hydroxylgroups of the starting flavonoids, while at the same time making itpossible to promote the transport of these esters through biologicalmembranes.

Within the framework of the invention, it has been possible to discover,totally unexpectedly, that the esterases present in cell tissues,particularly in the epidermis, are capable of cleaving one or more estergroups thus formed in the flavonoid esters of the invention and ofregenerating the starting flavonoids as well as the organic monoacidused.

Therefore the invention makes it possible to use the flavonoids releasedin this way, having their own, preserved activity (activities), incombination with the organic monoacids, which can thus act in asynergistic manner.

Insofar as this organic monoacid, for example sorbic acid or ascorbicacid, has its own activity, the invention enables the activity of thisacid to be combined with the activity of the flavonoid.

The flavonoid esters according to the invention can be used as cosmeticagents.

In this context, the flavonoid esters according to the invention aregenerally mixed with a cosmetically acceptable excipient, vehicle orcarrier. The amount of the flavonoid esters according to the inventionwhich is effective for a cosmetic activity is generally between 0.0001%and 10% by weight, preferably between 0.01 and 5% by weight, based onthe final weight of the cosmetic composition. The advantageous cosmeticactivity of the flavonoid esters according to the invention is based ona free radical inhibiting activity, an antioxidizing activity, aninhibiting activity on blotchiness, an inhibiting effect on chemical,physical or actinic erythema, a treatment for sensitive skin, a drainingtreatment, a slimming treatment, an anti-wrinkle treatment, astimulating effect on the synthesis of the components of theextracellular matrix, particularly elastin, a toning effect, animproving effect on the elasticity of the skin or the epidermis, and ananti-ageing effect.

By virtue of the liposoluble property of the flavonoid esters accordingto the invention, these flavonoid esters can easily be incorporated intoconventional cosmetic formulations, especially those in the form ofcreams, ointments, emulsions, gels or lotions. The flavonoid esters canbe used in the free state or in the encapsulated state, particularly bybeing at least partially incorporated in liposomes.

According to the invention, the above-mentioned flavonoid esters canalso be used in dietetics or in agri-foodstuff compositions.

The flavonoid esters according to the invention make it possible toimprove the stability of foodstuffs by virtue of their free radicalinhibiting and antioxidizing activity. Agri-foodstuff compositions whichmay be mentioned are drinks, fruit juices, tonic drinks and dairyproducts.

The invention also makes it possible to prepare pharmaceuticalcompositions.

In this context, the dosage used is that which is normally recommendedfor flavonoids when considering their known activities.

In the context of application to the epidermis, it will be preferable touse topical pharmaceutical compositions in which the flavonoid estersaccording to the invention will be mixed with a pharmaceuticallyacceptable excipient compatible with the epidermis. These pharmaceuticalcompositions can thus be formulated to have a tonic effect on the veins,for example in the form of an ointment, to increase the strength of theblood capillaries, to obtain an inhibiting effect on blotchiness or tohave an inhibiting effect on chemical, physical or actinic erythema.

The invention further relates to a method of cosmetic or pharmaceuticaltreatment which comprises applying, to any mammal and preferably a humanbeing in need thereof, a cosmetically or therapeutically effectiveamount of at least one flavonoid ester mentioned above, particularly bythe topical route.

In one advantageous embodiment, a cosmetic treatment is carried out.

In another advantageous embodiment of the invention, a therapeutictreatment is carried out.

Other objects, characteristics and advantages of the invention willbecome clearly apparent from the following Examples, which are given byway of illustration and cannot therefore in any way limit the scope ofthe invention.

In the Examples, all the percentages are given by weight, unlessindicated otherwise, the temperature is given in °C. or is roomtemperature and the pressure is atmospheric pressure, unless indicatedotherwise.

The most widely tested products are hesperitin, quercetin andhesperidin, rendered lipophilic by palmitic acid (C16), lauric acid(C12) and butyric acid (C4).

EXAMPLE 1

Quercetin (flavonol family) pentaacylated by C12

5 g of flavonoid (16.55 mmol) are placed in a dry 1 l round-bottomedflask and 200 ml of toluene are added. Lauroyl chloride (165.5 mmol) andthen saturated K₂CO₃ solution are added. The solution is refluxed for 1h. The toluene phase is separated off and the aqueous phase is extractedwith chloroform. Both the toluene and chloroform phases are washed withsaturated aqueous NaCl solution and then dried over sodium sulfate andconcentrated. The crude product obtained (13 g) is purified on silicagel (700 g) using chloroform/hexane (50/50) and then chloroform as theeluents. The product fractions are combined, concentrated and dried on avacuum pump for 24 h to give 10.83 g of quercetin pentaacylated by C12(yellow powder). Yield: 54%.

EXAMPLE 2

Quercetin pentaacylated by C12

165.5 mmol of lauroyl chloride are added to 5 g of quercetin (16.55mmol) in 100 ml of pyridine. The mixture is heated at 100° C. for 6hours. The solution is concentrated under vacuum and the crude productis dissolved in 200 ml of dichloromethane. After washing with aqueoussolutions of CuSO₄ and then NaCl, the solution is dried over Na₂SO₄ andthen concentrated. The crude product (16 g) is purified on a column ofsilica (800 g) using dichloromethane/hexane (2/3) as the eluent to give12.23 g of quercetin pentaacylated by C12. Yield: 61%.

EXAMPLE 3

Quercetin pentaacylated by C16

5 g of flavonoid (16.55 mmol) are placed in a dry 1 l round-bottomedflask and 200 ml of toluene are added. Palmitoyl chloride (165.5 mmol)and then saturated K₂CO₃ solution (100 ml) are added. The solution isrefluxed for 1 h. The toluene phase is separated off and the aqueousphase is extracted with chloroform. Both the toluene and chloroformphases are washed with saturated aqueous NaCl solution and then driedover sodium sulfate and concentrated. The crude product obtained (19.3g) is purified on silica gel (500 g) using chloroform/hexane (50/50) andthen chloroform as the eluents. The product fractions are combined,concentrated and dried on a vacuum pump for 24 h to give 12.84 g ofquercetin pentaacylated by C16 (white powder). Yield: 52%.

EXAMPLE 4

Quercetin pentaacylated by C16

165.5 mmol of palmitoyl chloride are added to 5 g of quercetin (16.55mmol) in 100 ml of pyridine. The mixture is heated at 100° C. for 6hours. The solution is concentrated under vacuum and the crude productis dissolved in 200 ml of dichloromethane. After washing with solutionsof CuSO₄ and then NaCl, the solution is dried over Na₂SO₄ and thenconcentrated. The crude product (17.6 g) is purified on a column ofsilica (800 g) using dichloromethane/hexane (1/3) as the eluent to give14.3 g of quercetin pentaacylated by C16. Yield: 58%.

EXAMPLE 5

Quercetin pentaacylated by C4

The protocol of Example 2 is followed with 5 g of quercetin and 165.5mmol of butyric anhydride; the crude product (8.34 g) is purified on acolumn of silica (700 g) using CHCl₃/hexane (2/3) as the eluent to give5.18 g of quercetin pentaacylated by C4. Yield: 48%.

EXAMPLE 6

Hesperitin (flavanone family) diacylated by C12

5 g of flavonoid (16.55 mmol) are placed in a dry 1 l round-bottomedflask and 200 ml of toluene are added. Lauroyl chloride (26.5 mmol) andthen saturated aqueous K₂CO₃ solution (100 ml) are added. The solutionis refluxed for 1 h. The toluene phase is separated off and the aqueousphase is extracted with chloroform. Both the toluene and chloroformphases are washed with saturated aqueous NaCl solution and then driedover sodium sulfate and concentrated. The crude product obtained (10.8g) is purified on silica gel (500 g) using dichloromethane/hexane (1/4)and then chloroform as the eluents. The product fractions are combined,concentrated and dried on a vacuum pump for 24 h to give 7.1 g ofhesperitin diacylated by C12 (oil). Yield: 64%.

EXAMPLE 7

Hesperitin monoacylated by C12

5 g of flavonoid (16.55 mmol) and 70 ml of chloroform are placed in adry 1 l round-bottomed flask. Lauroyl chloride (3.85 ml, 16.55 mmol) andthen pyridine (1.88 ml, 16.55 mmol) are added and the reaction mixtureis then refluxed for 15 h. After dilution with 150 ml of chloroform, theorganic phase is separated off, washed with aqueous NaCl solution, driedover Na₂SO₄ and concentrated to give 11.28 g of a red oil. Purificationof the crude product on a column of silica (400 g) using dichloromethaneas the eluent gives 1.98 g of hesperitin diacylated by C12 (yield: 18%)and 0.81 g of hesperitin monoacylated by C12 (yield: 10%).

EXAMPLE 8

Hesperitin monoacylated by C12

5 g of flavonoid (16.55 mmol) and 100 ml of pyridine are placed in a dry1 l round-bottomed flask, followed by 16.55 mmol of lauroyl chloride.The solution is stirred at ordinary temperature for 1 hour andevaporated to dryness. The crude product is dissolved in 200 ml ofchloroform, washed with CuSO₄ solution and then with aqueous NaClsolution, dried over Na₂SO₄ and concentrated to give 8.92 g of a crudeproduct, which is chromatographed on a column of silica (400 g) usingdichloromethane as the eluent to give 2.74 g of hesperitin diacylated byC12 (yield: 25%) and 0.96 g of hesperitin monoacylated by C12 (yield:12%). These products can be used in the form of the crude product, inthe form of the product purified in the mixture or in the form ofproducts purified independently.

EXAMPLE 9

Hesperitin monoacylated and diacylated by C12

The protocol of Example 2 is followed with 5 g of hesperitin and 16.55mmol of lauroyl chloride; the crude product (8.92 g) is not purified; itcontains hesperitin monoacylated and diacylated by C12 (yield: 37%) andis used as such.

EXAMPLE 10

Hesperitin monoacylated and diacylated by C16

The protocol of Example 2 is followed with 5 g of hesperitin and 16.55mmol of palmitoyl chloride; the crude product (10.3 g) is purified on acolumn of silica (600 g) using CH₂Cl₂/hexane (1/1) and CH₂Cl₂ as theeluents to give 2.7 g of hesperitin diacylated by C16 (yield: 21%) and0.89 g of hesperitin monoacylated by C16 (yield: 10%), which can be usedin the form of the crude product, in the form of the product purified inthe mixture or in the form of products purified independently.

EXAMPLE 11

Hesperitin triacylated by C16

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of palmitoyl chloride; the crude product is purified on a column ofsilica (500 g) using CH₂Cl₂/hexane (1/1) as the eluent to give 10 g ofhesperitin triacylated by C16. Yield: 59.4%.

EXAMPLE 12

Hesperitin triacylated by C4

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of butyric anhydride; the crude product (13 g) is purified on acolumn of silica (700 g) using CHCl₃/hexane (2/3) as the eluent to give4.61 g of hesperitin triacylated by C4. Yield: 55%.

EXAMPLE 13

Hesperitin triacylated by C18:0

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of stearoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C18:0.

EXAMPLE 14

Hesperitin triacylated by C18:1

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of oleoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C18:1.

EXAMPLE 15

Hesperitin triacylated by C18:2

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of linoleoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C18:2.

EXAMPLE 16

Hesperitin triacylated by C18:3

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of linolenoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C18:3.

EXAMPLE 17

Hesperitin triacylated by C11:1

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of undecylenoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C11:1.

EXAMPLE 18

Hesperifin triacylated by C7

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of heptanoyl chloride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated by C7.

EXAMPLE 19

Hesperitin triacylated by succinic acid

The protocol of Example 2 is followed with 5 g of hesperitin and 99.3mmol of succinic anhydride; the crude product can be used as such orpurified on a column of silica to give hesperitin triacylated bysuccinic acid.

EXAMPLE 20

Acylated ester of apigenin of the flavone family

In this Example the procedure is as described in Example 6 except thatthe hesperitin is replaced with apigenin.

Triacylated apigenin is obtained. It should be noted that apigenin is acompound of formula (II) containing 3 OH groups.

Manufacturing variants can be carried out by using different reactionconditions or by changing the nature of the acid used, as in Examples 7to 19.

EXAMPLE 21

Acylated ester of naringenin of the flavanone family, like hesperitin

An acylated ester of naringenin can be prepared by using the reactionconditions of any one of Examples 6 to 19 except that the hesperitin isreplaced with naringenin. A triacylated derivative is obtained.

EXAMPLE 22

Hesperidin (glycosylated flavanone family) octaacylated by C12

The protocol of Example 2 is followed with 5 g of hesperidin and 131.02mmol of lauroyl chloride; the crude product (15 g) can be purified on acolumn of silica to give hesperidin octaacylated by C12.

EXAMPLE 23

Palmitic acid ester of hesperidin of the glycosylated flavanone family

The title palmitate ester of this Example is obtained by following theprocedure described in Example 22 except that the lauroyl chloride isreplaced with palmitoyl chloride.

EXAMPLE 24

Flavonoid ester of naringin of the glycosylated flavanone family, likehesperidin

An acylated ester of naringin is prepared by using the reactionconditions of Example 22 except that the hesperidin is replaced withnaringin.

EXAMPLE 25

Acylated ester of diosmin of the glycosylated flavone family

An acylated ester of diosmin, for example diosmin acylated with lauricacid, can be prepared by using the reaction conditions of Example 6 andreplacing the hesperitin with diosmin.

EXAMPLE 26

Acylated ester of rutin of the glycosylated flavonol family

A lauric acid ester of rutin can be prepared by using the reactionconditions of Example 6.

In the case of Examples 23 to 26 it is also possible to change theesterifying acid or the reaction conditions, as in the variants formingthe subject of Examples 7 to 19.

EXAMPLE 27

Oxidation stability test on flavonoids in simple preparations

A solution of hesperitin containing 31.1 g/l (i.e. 0.103 M) is preparedin ethoxy-diglycol. The pH is adjusted to 5 or 6 and then 10 g/l of apreservative based on parabens are added to the mixture in order toavoid bacterial pollution. In a separate procedure, the product of theinvention resulting from Example 9 is also made up into a 0.103 Msolution in ethoxydiglycol, the pH is adjusted to 5 or 6 and then 10 g/lof a preservative based on parabens are again added to the mixture. Atidentical molar concentrations, the two products are therefore comparedfor their oxidation stability, the color parameters being used as thestability indicators. The color references given in the Examples whichfollow refer to the Pantone colors as used in all the paint color chartswell known to those skilled in the art.

TABLE I Color of the solutions 1 day after manufacture: Acylatedhesperitin according to Hesperitin Example 9 of the invention 20° C. 4°C. 45° C. 20° C. 4° C. 45° C. pH 5 157C 157C 157C 1205C 120C 120C orangeto orange to orange to very light brown brown brown yellow pH 6 157C157C 157C 1215C 120C 113C orange to orange to orange to light brownbrown brown yellow

TABLE II Color of the solutions 21 days after manufacture: Acylatedhesperitin according to Hesperitin Example 9 of the invention 20° C. 4°C. 45° C. 20° C. 4° C. 45° C. pH 5 black + black + black + 1205C 1205C120C precipitate precipitate precipitate very light yellow pH 6 black +black + black + 1215C 1205C 121C precipitate precipitate precipitatelight yellow

Here, rendering the flavonoids lipophilic by acylation can therefore bea means of stabilizing these substances towards oxidation.

EXAMPLE 28

Oxidation stability test on flavonoids in complex preparations(emulsions)

Composition of the formulation:

Phase INCI name g/100 g A water gsp 100 B PEG2 stearate SE, ceteareth25, hydrogenated 16.0  coconut oil, mineral oil C water 3.0polyacrylamide, isoparaffin, laureth-7 1.0 D phenoxyethanol,methylparaben, ethylparaben, 1.0 propylparaben, butylparaben butyleneglycol 1.0 E ethoxydiglycol with or without free flavonoid, with 0.01-40or without product of the invention

TABLE III Stability test: Product of the Product of the inventioninvention according to according to Hesperitin Example 9 HersperitinExample 9 Cream Control 520 μM 520 μM 1043 μM 1043 μM pH 6.94 6.76 6.976.9 6.9 T 1 day white light beige white more white pronounced beige T 7days white yellow very slight very yellow yellow glints +++ yellowglints +++++ T 25 days white yellow very slight very yellow yellowglints +++ yellow glints +++++ T 35 days white yellow very slight veryyellow yellow glints ++++ yellow glints ++++++

After studying the stabilities over about 1 month, it can be said thatthe color of the formulations containing flavonoids used in the formwhich has not been rendered lipophilic undergoes an extremelyunfavorable change at 45° C.

The formulation whose color stability is the closest to that of thecontrol is the one containing 520 μmol/l of flavonoid which has beenrendered lipophilic.

At constant molarities, the creams containing flavonoids which have beenrendered lipophilic are more stable than those containing flavonoids, aphenomenon which is accentuated when the flavonoid is introduced inexcess into the cream. Rendering the flavonoids lipophilic thereforestabilizes the color in emulsions.

EXAMPLE 29

Determination of the anti-elastase activity

The enzymatic substrate elastin-rhodamine is dissolved in TrisHCl buffer(31.52 g of TrisHCl, water qsp 1000 ml) of pH 8.8 at a rate of 15 mg/ml.1 mg of human leukocytic elastase is dissolved in 20 ml of TrisHClbuffer. The products of the invention are evaluated for their capacityto inhibit the degradation of elastin, which can be followed byfluorescence (excitation at 530 nm; emission at 590 nm) after theincubation, for 20 min at 37° C., of a mixture comprising the substrate,the enzyme and the inhibitor to be tested. The results are given as %inhibition relative to the inhibitor-free control. The products of theinvention of Example 7 and Example 9, and the unmodified flavonoid, aresolubilized in ethoxydiglycol:

TABLE IV Anti-elastase test: Test concentration Product of the Productof the (mol/l) Hesperitin invention (Ex. 7) invention (Ex. 9) 0.103 100100 100 1.03⁻³ 20 50 44 1.03⁻⁴ 24 36 38 1.03⁻⁵ 0 34 34

The products of the invention of Example 6, and the unmodifiedflavonoid, are solubilized in ethoxydiglycol:

TABLE V Anti-elastase test: Product of the invention Test concentration(mol/l) Hesperitin (Ex. 6) 0.103 100 100 1.03⁻³ 20 65 1.03⁻⁵ 0 29

The anti-elastase activity is stronger for the flavonoids which havebeen rendered lipophilic than for the flavonoids before they have beenrendered lipophilic.

EXAMPLE 30

Determination of the free radical inhibiting activity in vitro

A 60 μM solution of 1,1-diphenyl-2-picrylhydrazyl in ethanol is placedin contact, for 30 minutes at room temperature, with a sampleoriginating from the products of the invention whose free radicalinhibiting power is to be determined. The drop in absorbance is thenmeasured at 520 nm and the results are given as the percentage decreasein OD caused by the test compound relative to the solvent used. Thehigher the percentage decrease, the stronger will be the free radicalinhibiting activity of the active ingredient tested.

The products of the invention are dissolved in DMSO; the results (DMSOcontrol subtracted) are given as % free radical inhibiting activity asdescribed above:

TABLE VI Compound at 25 mM Free radical inhibiting activity Hesperitin42% Product of Example 6 67%

The products of the invention are dissolved in ethoxydiglycol; theresults (ethoxy-diglycol control subtracted) are given as % free radicalinhibiting activity as described above:

TABLE VII Product of the Product of the invention inventionConcentration according according in mol/l Hesperitin to Example 8 toExample 9 0.103 94 93 95 1.03⁻³ 28 10 17 1.03⁻⁵  8  6 12

The free radical inhibiting activity is preserved after the flavonoidshave been rendered lipophilic, which is totally unexpected for thoseskilled in the art.

EXAMPLE 31

Use of the products of the invention in cosmetic or pharmaceuticalformulations of the oil-in-water emulsion type

Formulation 31a A Water qsp 100 Butylene glycol 2 Glycerol 3 Sodiumdihydroxycetyl phosphate, 2 isopropyl hydroxycetyl ether Butyleneglycol, methylparaben, 2 ethylparaben, propylparaben Products of theinvention 0.0001-5% B Glycol stearate SE 14  Triisononanoin 5 Octylcocoate 6 Formulation 31b Water qsp 100 Butylene glycol 2 Glycerol 3Polyacrylamide, isoparaffin, laureth-7   2.8 Butylene glycol,methylparaben, 2 ethylparaben, propylparaben Phenoxyethanol,methylparaben, 2 propylparaben, butylparaben, ethylparaben Butyleneglycol   0.5 Products of the invention 0.0001-5% Formulation 31c ACarbomer   0.50 Propylene glycol 3 Glycerol 5 Water qsp 100 B Octylcocoate 5 Bisabolol   0.30 Dimethicone   0.30 C Sodium hydroxide   1.60D Phenoxyethanol, methylparaben,   0.50 propylparaben, butylparaben,ethylparaben E Perfume   0.3 F Products of the invention 0.0001-5%

EXAMPLE 32 OF THE INVENTION

Use of the products of the invention in a formulation of thewater-in-oil type

A PEG 30 dipolyhydroxystearate 3 Capric triglycerides 3 Cetearyloctanoate 4 Dibutyl adipate 3 Grape seed oil 1.5 Jojoba oil 1.5Phenoxyethanol, methylparaben, 0.5 propylparaben, butylparaben,ethylparaben B Glycerol 3 Butylene glycol 3 Magnesium sulfate 0.5 EDTA0.05 Water qsp 100 C Cyclomethicone 1 Dimethicone 1 D Perfume 0.3 EProduct of the invention 0.0001-5%

EXAMPLE 33 OF THE INVENTION

Use of the products of the invention in a formulation of the shampoo orshower gel type

A Xanthan gum 0.8 Water qsp 100 B Butylene glycol, methylparaben, 0.5ethylparaben, propylparaben Phenoxyethanol, methylparaben, 0.5propylparaben, butylparaben, ethylparaben C Citric acid 0.8 D Sodiumlaureth sulfate 40.0 E Product of the invention 0.0001-1%

EXAMPLE 34 OF THE INVENTION

Use of the products of the invention in a formulation of the lipstick orother anhydrous product type

A Mineral wax 17.0 Isostearyl isostearate 31.5 Propylene glycoldipelargonate 2.6 Propylene glycol isostearate 1.7 PEG 8 beeswax 3.0Hydrogenated palm kernel oil, glycerides, 3.4 hydrogenated palmglyceride Lanolin oil 3.4 Sesame oil 1.7 Tribehenin 1.7 Cetyl lactate1.7 Mineral oil, lanolin alcohol 3.0 B Castor oil qsp 100 Titaniumdioxide 3.9 CI 15850:1 0.616 CI 45410:1 0.256 CI 19140:1 0.048 CI 774912.048 C Product of the invention 0.0001-5

EXAMPLE 35 OF THE INVENTION

Use of the products of the invention in an aqueous gel formulation (eyecontour gels, slimming gels, etc.)

Water qsp 100 Carbomer 0.5 Butylene glycol 15 Phenoxyethanol,methylparaben, 0.5 propylparaben, butylparaben, ethylparaben Product ofthe invention 0.0001-5

EXAMPLE 36

Toxicological studies carried out on the product of the invention ofExample 9

The product of Example 9 (6 g) is dissolved in ethoxydiglycol (93 g),and 1 g of a mixture containing different parabens, used as bacterialpreservatives, is added to the mixture. This preparation is used for thefollowing toxicity studies:

a) Oral toxicity

The tests were performed by the protocol in accordance with the OECDguideline relating to the study of acute oral toxicity (no. 401 of Feb.24, 1987), at maximum doses of 5 g/kg body weight, and did not cause anymacroscopic lesions attributable to a toxic effect of the product. Theabove preparation, manufactured from the products of the invention andused orally at a dose below 5 g/kg, therefore has zero toxicity.

b) Eye irritation

The tests were performed by the official method in accordance with thedecree of May 3, 1990 (Official Journal of the French Republic of Nov.14, 1990) with the above-described preparation and did not cause anylesions of the iris or cornea. The above preparation, manufactured fromthe products of the invention and instilled pure, appeared to benon-irritant and the eye tolerance can be considered to be very good.

c) Skin irritation

The tests were performed by the official method in accordance with thedecree of Feb. 1, 1982 (Official Journal of the French Republic of Feb.21, 1982) with the products of the invention (Examples 12 and 15) anddid not cause any irritation phenomena.

The above preparation, manufactured from the products of the inventionand instilled pure, appeared to be non-irritant and the skin tolerancecan be considered to be excellent.

d) Testing for the sensitizing power

Maximization tests were performed by a protocol adapted from the methoddescribed by Magnusson and Kligman (J. INVEST. DERM. 1969, 52, 268-276).The above preparation, manufactured from the products of the inventionand instilled pure, did not cause any macroscopic reactions indicativeof a sensitization reaction. The products of the invention can thereforebe considered to be hypo-allergenic (class I).

What is claimed is:
 1. A method of providing cosmetic care comprisingthe topical application, to at least one zone of the skin of a person inneed thereof, of a cosmetically effective amount of at least oneflavonoid ester consisting essentially of the reaction product of: a) atleast one flavonoid with a ketone group in the 4-position, saidflavonoid component being selected from the group consisting of aflavonoid with a ketone group in the 4-position, a salt of saidflavonoid, an ester of said flavonoid, an ether of said flavonoid, aC-heteroside of said flavonoid, and an O-heteroside of said flavonoid,said flavonoid with a ketone group in the 4-position having thefollowing structural chemical formula (I) or (II):

in which: -the groups (OR₁) to (OR₄) are in any position on the ring;-in formula (I), A is a hydrogen atom, a substituent R, a group —OH or agroup —OR, and in formula (II), A is a hydrogen atom, a substituent R,or a group —OH, R being as defined for the radicals R₁ to R₄; -n₁ andn₂, which are identical or different from one another, are integers from0 to 4, the total of n₁+n₂ being equal to at most 4, corresponding tothe maximum number of substitutions on the ring; -n₃ and n₄, which areidentical or different from one another, are integers from 0 to 5, thetotal of n₃ +n₄ being equal to a maximum of 5, representing the maximumnumber of substitutions on the ring; and -R₁, R₂, R₃ and R₄ are eachindependently a hydrogen atom, an alkyl group having from 1 to 30 carbonatoms, an acyl group with an alkyl radical having from 1 to 30 carbonatoms, an ose unsubstituted, an ose substituted by a hydrocarbon chainhaving from 1 to 30 carbon atoms, under the proviso that at least one ofthe substituents R is a hydrogen atom, thereby defining one freehydroxyl group; and the isomers of said esters; with b) an organicmonoacid having from 3 to 30 carbon atoms.
 2. The method of claim 1,wherein the flavonoid component is a non-glycosylated flavone.
 3. Themethod of claim 2, wherein said non-glycosylated flavone is of formulaII.
 4. The method of claim 1, wherein the flavonoid component is anon-glycosylated flavone selected from the group consisting of apigenol,apigenin, and luteolol.
 5. The method of claim 1, wherein the flavonoidcomponent is a glycosylated flavone.
 6. The method of claim 5, whereinsaid glycosylated flavone is selected from the group consisting ofdiosmin, orientin, saponarin, and shaftoside.
 7. The method of claim 1,wherein said flavonoid component is a non-glycosylated flavonol.
 8. Themethod of claim 7, wherein said non-glycosylated flavonol is selectedfrom the group consisting of kaempferol and quercertol.
 9. The method ofclaim 1, wherein the flavonoid component is a glycosylated flavonol. 10.The method claim 9, wherein said glycosylated flavonol is selected fromthe group consisting of rutin, quercitroside, hyperoside, andisoquercitroside.
 11. The method of claim 1, wherein said flavonoidcomponent is selected from the group consisting from a non-glycosylateddihydroflavonol and a glycosylated dihydroflavonol.
 12. The method ofclaim 11, wherein said dihydroflavonol is selected from the groupconsisting of dihydrokaempferol and dihydroquercetol.
 13. The method ofclaim 1, wherein the flavonoid component is a non-glycosylated flavone.14. The method of claim 1, wherein the flavonoid component is anon-glycosylated flavanone selected from the group consisting ofnaringetol, eriodictyol, hesperitin, eucalyptin, cirsimaritin,cajaflavanone, hinokiflavone, and amentaflavanone.
 15. The method ofclaim 1, wherein the flavonoid component is a glycosylated flavanone.16. The method of claim 15, wherein the glycosylated flavanone isselected from hesperidin and naringin.
 17. The method of claim 1,wherein the organic monoacid is selected from the group consisting ofbutyric acid (C4:0); valeric acid (C5:0), hexanoic acid (C6:)), sorbicacid (C6:2), ascorbic acid, lauric acid (C12), palmitic acid (C16:0),stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2),linolenic acid (C18:3), undecylenic acid (C11:1), heptanoic acid (C7:0),arachidonic acid (C20:4), eicosapentanoic acid (C20:5), anddocosahexanoic acid (C22:6 and C24:1).
 18. The method of claim 1,wherein the flavonoid component is substituted by an ose selected fromthe group consisting of shamnose, glactose, glucose and arabinose, whichmay or may not be substituted; said heteroside is selected fromtiliroside, orientin, shaftoside, saponarin, rutin, hesperidin, anddiosmin.
 19. The method of claim 1, wherein at least one of saidsubstituents R₁ to R₄ is selected from the group consisting of asaturated C₁₋₆ alkyl group, an unsaturated C₁-C₆ alkyl group, a linearC₁-C₆ alkyl group, a branched C₁-C₆ alkyl group, a cyclic C₁-C₆ alkylgroup, and an acyl group having an alkyl radical from 1 to 8 carbonatoms.
 20. A method of providing cosmetic care with an anti-elastaseactivity, comprising the topical application, to at least one zone ofthe skin of a person in need thereof, of a cosmetically anti-elastaseeffective amount of at least one flavonoid ester consisting essentiallyof the reaction product of: a) at least one flavonoid component selectedfrom the group consisting of a flavonoid with a ketone group in the4-position, a salt of said flavonoid, and ester of said flavonoid, anether of said flavonoid, a C-heteroside of said flavonoid, and anO-heteroside of said flavonoid, said flavonoid with a ketone group inthe 4-position having the following structural chemical formula (I) or(II):

in which: -the groups (OR₁) to (OR₄) are in any position on the ring; -Ais a hydrogen atom, a substituent R, a group —OH or a group —OR, R beingas defined for the radicals R₁ to R₄; -n₁ and n₂, which are identical ordifferent from one another, are integers from 0 to 4, the total of n₁+n₂being equal to at most 4, corresponding to the maximum number ofsubstitutions on the ring; -n₃ and n₄, which are identical or differentfrom one another, are integers fromn 0 to 5, the total of n₃+n₄ beingequal to a maximum of 5, representing the maximum number ofsubstitutions on the ring; and -R₁, R₂, R₃ and R₄ are each independentlya hydrogen atom, an alkyl group having from 1 to 30 carbon atoms, anacyl group with an alkyl radical having from 1 to 30 carbon atoms, anose unsubstituted, an ose substituted by a hydrocarbon chain having from1 to 30 carbon atoms, under the proviso that at least one of thesubstituents R is a hydrogen atom, thereby defining at least one freehydroxyl group; and the isomers of said esters; with b) an organicmonoacid having from 3 to 30 carbon atoms.
 21. The method of claim 20,wherein the flavonoid component is a non-glycosylated flavone.
 22. Themethod of claim 21, wherein said non-glycosylated flavone is of formula(II).
 23. The method of claim 20, wherein the flavonoid component is anon-glycosylated flavone selected from the group consisting of apigenol,apigenin, and luteolol.
 24. The method of claim 20, wherein theflavonoid component is a glycosylated flavone.
 25. The method of claim24, wherein said glycosylated flavone is selected from the groupconsisting of diosmin, orientin, saponarin, and shaftoside.
 26. Themethod of claim 20, wherein the flavonoid component is anon-glycosylated flavonol.
 27. The method of claim 26, wherein saidnon-glycosylated flavonoid is selected from the group consisting ofkaempferol and quercetol.
 28. The method of claim 20, wherein theflavonoid component is a glycosylated flavonol.
 29. The method of claim28, wherein said glycosylated flavonol is selected from the groupconsisting of rutin, quercitroside, hyperoside, isoquercitroside. 30.The method of claim 20, wherein said flavonoid component is selectedfrom the group consisting of a non-glycosylated dihydroflavonol and aglycosylated dihydroflavonol.
 31. The method of claim 30, wherein saiddihydroflavonol is selected from the group consisting ofdihydrokaempferol and dihydroquercetol.
 32. The method of claim 20,wherein the flavonoid component is a non-glycosylated flavanone.
 33. Themethod of claim 20, wherein the flavonoid component is anon-glycosylated flavanone selected from the group consisting ofnaringetol, eriodictyol, hesperitin, eucalyptin, cirsimaritin,cajaflavanone, hinokiflavone and amentaflavanone.
 34. The method ofclaim 20, wherein the flavonoid component is a glycosylated flavanone.35. The method of claim 34, wherein said glycosylated flavanone isselected from hesperidin and naringin.
 36. The method of claim 20,wherein the organic monoacid is selected from the group consisting ofbutyric acid (C4:0), valeric acid (C5:0), hexanoic acid (C6:0), sorbicacid (C6:2). ascorbic acid, lauric acid (C12), palmitic acid (C16:0),stearic acid (C18:0), oleic acid (C18:1) linoleic acid (C18:2),linolenic acid (C18:3), undecylenic acid (C11:1), heptanoic acid (C7:0),arachidonic acid (C20:4), eicosapentanoic acid (20:5) and docosahexanoicacid (C22:6 and C24:1).
 37. The method of claim 1, wherein the flavonoidcomponent is substituted by an ose selected from the group consisting ofa rhamnose, galactose, glucose and arabinose, which may or may not besubstituted; said heteroside is selected from tiliroside, orientin,shaftoside, saponarin, rutin, hesperidin and diosmin.
 38. The method ofclaim 1, wherein at least one of said substituents R₁ to R₄ is selectedfrom the group consisting of a saturated C₁₋₆ alkyl group, anunsaturated C₁-C₆ alkyl group, a linear C₁-C₆ alkyl group, a branchedC₁-C₆ alkyl group, a cyclic C_(1-C) ₆ alkyl group, and an acyl grouphaving an alkyl radical from 1 to 8 atoms.
 39. A method of providingcosmetic care with free radical inhibiting activity, comprising thetopical application, to at least one zone of the skin of a person inneed thereof, of a cosmetically anti-elastase effective amount of aflavonoid ester consisting essentially of the reaction product of: a) atleast on flavonoid component selected from the group consisting of aflavonoid with a ketone group in the 4-position, a salt of saidflavonoid, an ester of said flavonoid, an ether of said flavonoid, aC-heteroside of said flavonoid, and an O-heteroside of said flavonoid,said flavonoid with a ketone group in the 4-position having thefollowing structural chemical formula (I) or (II):

in which: -the groups (OR₁) to (OR₄) are in any position on the ring;-in formula (I), A is a hydrogen atom, a substituent R, a group —OH or agroup —OR, and in formula (II), A is a hydrogen atom, a substituent R,or a group —OH, R being as defined for the radicals R₁ to R₄; -n₁ andn₂, which are identical or different from one another, are integers from0 to 4, the total of n₁+n₂ being equal to at most 4, corresponding tothe maximum number of substitutions on the ring; -n₃ and n₄, which areidentical or different from one another, are integers from 0 to 5, thetotal of n₃+n₄ being equal to a maximum of 5, representing the maximumnumber of substitutions on the ring; and -R₁, R₂, R₃ and R₄ are eachindependently a hydrogen atom, an alkyl group having from 1 to 30 carbonatoms, an acyl group with an alkyl radical having from 1 to 30 carbonatoms, an ose unsubstituted, an ose substituted by a hydrocarbon chainhaving from 1 to 30 carbon atoms; under the proviso that at least one ofthe substituents R is a hydrogen atom, thereby defining at least onefree hydroxyl group; and the isomers of said esters; with b) an organicmonoacid having from 3 to 30 carbon atoms.
 40. The method of claim 39,wherein the flavonoid component is a non-glycosylated flavone.
 41. Themethod of claim 40, wherein said non-glycosylated flavone is of formulaII.
 42. The method of claim 39, wherein the flavonoid component is anon-glycosylated flavone selected from the group consisting of apigenol,apigenin, and luteolol.
 43. The method of claim 39, wherein theflavonoid component is a glycosylated flavone.
 44. The method of claim43, wherein said glycosylated flavone is selected from the groupconsisting of diosmin, orientin, saponarin, and shaftoside.
 45. Themethod of claim 39, wherein said flavonoid component is anon-glycosylated flavonol.
 46. The method of claim 45, wherein saidnon-glycosylated flavonoid is selected from the group consisting ofkaempferol and quercetol.
 47. The method of claim 39, wherein theflavonoid component is a glycosylated flavonol.
 48. The method of claim47, wherein said glycosylated flavonol is selected from the groupconsisting of rutin, quercitroside, hyperoside, and isoquercitroside.49. The method of claim 39, wherein said flavonoid component is selectedfrom the group consisting of a non-glycosylated dihydroflavonol and aglycosylated dihydroflavonol.
 50. The method of claim 49, wherein saiddihydroflavonol is selected from the group consisting ofdihydrokaempferol and dihydroquercetol.
 51. The method of claim 39,wherein the flavonoid component is a non-glycosylated flavanone.
 52. Themethod of claim 39, wherein the flavonoid component is anon-glycosylated flavanone selected from the group consisting ofnaringetol, eriodictyol, hesperitin, eucalyptin, cirsimaritin,cajaflavanone, hinokiflavone, and amentaflavanone.
 53. The method ofclaim 39, wherein the flavonoid component is a glycosylated flavanone.54. The method of claim 53, wherein said glycosylated flavanone isselected from hesperidin and naringin.
 55. The method of claim 39,wherein the organic monoacid is selected from the group consisting ofbutyric acid (C4:0), valeric acid (C5:0), hexanoic acid (C6:0), sorbicacid (C6:2), ascorbic acid, lauric acid (C12), palmitic acid (C16:0),stearic acid (C18:0), oleic acid (18:1), linoleic acid (C18:2),linolenic acid (C18:3), undecylenic acid (C11:1), heptanoic acid (C7:0),arachidonic acid (C20:4), eicosapentanoic acid (C20:5) anddocosahexanoic acid (C22:6 and C24:1).
 56. The method of claim 39,wherein the flavonoid component is substituted by an ose selected fromthe group consisting of rhamnose, galactose, glucose and arabinose,which may or may not be substituted; said heteroside is selected fromtiliroside, orientin, shaftoside, saponarin, rutin, hesperidin anddiosmin.
 57. The method of claim 39, wherein at least one of saidsubstituents R₁ to R₄ is selected from the group consisting of asaturated C₁₋₆ alkyl group, an unsaturated C₁-C₆ alkyl group, a linearC₁-C₆ alkyl group, a branched C₁-C₆ alkyl group, a cyclic C₁-C₆ alkylgroup, and an acyl group having an alkyl radical from 1 to 8 carbonatoms.
 58. A method of providing cosmetic care selected from the groupconsisting of an anti-wrinkle effect, a stimulating effect on thesynthesis of components of the extracellular matrix, a toning effect,and an improving effect on the elasticity of the skin, comprising thetopical application, to zones of the skin of a person in need thereof,of an effective amount for said cosmetic care of at least one flavonoidester selected from the group consisting of quercetin laurylpentaacylated, quercetin palmityl pentaacylated, quercetinpentabutyrilacylated, hesperitin dilaurylacylated, hesperitinmonolaurylacylated, hesperitin dilaurylacylated, hesperitindipalmitylacylated, hesperitin tripalmitylacylated, hesperitintributyrilacylated, hesperitin tristearylacylated, hesperitintrioleoylacylated, hesperitin trilinoleoylacylated, hesperitintrilinolenoylacylated, hesperitin triundecylenoylacylated, hesperitinheptanoylacylated, hesperitin trisuccinylacylated, apigenintrilaurylacylated, naringenin triacylated, hesperidinoctalaurylacylated, hesperidin octapalmitylacylated, naringinoctalaurylacylated, diosmin laurylacylated and rutin laurylacylated. 59.A method of providing cosmetic care comprising the topical application,to at least one zone of the skin of a person in need thereof, of aneffective amount of at least one flavonoid ester selected from the groupconsisting of hesperitin dilaurylacylated, hesperitinmonolaurylacylated, hesperitin dilaurylacylated, hesperitindipalmitylacylated, hesperitin tripalmitylacylated, hesperitintributyrilacylated, hesperitin tristearylacylated, hesperitintrioleoylacylated, hesperitin trilinoleoylacylated, hesperitintrilinolenoylacylated, hesperitin triundecylenoylacylated, hesperitinheptanoylacylated, hesperitin trisuccinylacylated, apigenintrilaurylacylated, naringenin triacylated, hesperidinoctalaurylacylated, hesperidin octapalmitylacylated, naringinoctalaurylacylated, diosmin laurylacylated and rutin laurylacylated.